Faculty of Science and Engineering, Stratingh Institute for Chemistry, University of Groningen, 9747 AG Groningen, The Netherlands.
Department of Chemistry, University of Basel, BPR 1096, 4058 Basel, Switzerland.
Proc Natl Acad Sci U S A. 2023 Jul 4;120(27):e2301279120. doi: 10.1073/pnas.2301279120. Epub 2023 Jun 26.
The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS--PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.
纳米医学中响应性系统的设计源于当前分子药物递送中未解决的需求所带来的挑战。在这里,我们提出了一种具有高时空控制和可调释放特性的递药系统。该设计基于疏水性合成分子旋转马达和 PDMS-PMOXA 两亲嵌段共聚物的结合,以创建响应性自组装系统。通过低功率可见光(λ=430nm,6.9mW)的成功掺入和选择性激活,实现了高效率(高达 75%)的荧光染料递药。此外,我们证明了能够按需在连续循环中开启和关闭响应行为的能力。低浓度的光响应单元(低至分子马达的 1mol%)被证明可有效地促进释放。我们的系统还在使用肺癌细胞系和封装 FDA 批准药物的相关生理条件下进行了测试。与给予的游离药物相比,观察到相似水平的细胞活力,这表明我们的平台具有按需高效递药的潜力。这项工作为合成分子机器在下一代智能递药系统中的应用提供了重要的一步。